Elsevier

The Lancet

Volume 360, Issue 9335, 7 September 2002, Pages 743-751
The Lancet

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Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial

https://doi.org/10.1016/S0140-6736(02)09894-XGet rights and content

Summary

Background

Current guidelines suggest that, for patients at moderate risk of death from unstable coronary-artery disease, either an interventional strategy (angiography followed by revascularisation) or a conservative strategy (ischaemia-driven or symptom-driven angiography) is appropriate. We aimed to test the hypothesis that an interventional strategy is better than a conservative strategy in such patients.

Methods

We did a randomised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes (mean age 62 years, 38% women). Patients were assigned an early intervention or conservative strategy. The antithrombin agent in both groups was enoxaparin. The coprimary endpoints were a combined rate of death, non-fatal myocardial infarction, or refractory angina at 4 months; and a combined rate of death or non-fatal myocardial infarction at 1 year. Analysis was by intention to treat.

Findings

At 4 months, 86 (9·6%) of 895 patients in the intervention group had died or had a myocardial infarction or refractory angina, compared with 133 (14·5%) of 915 patients in the conservative group (risk ratio 0·66, 95% CI 0·51–0·85, p=0·001). This difference was mainly due to a halving of refractory angina in the intervention group. Death or myocardial infarction was similar in both treatment groups at 1 year (68 [7·6%] vs 76 [8·3%], respectively; risk ratio 0·91, 95% CI 0·67–1·25, p=0·58). Symptoms of angina were improved and use of antianginal medications significantly reduced with the interventional strategy (p<0·0001).

Interpretation

In patients presenting with unstable coronaryartery disease, an interventional strategy is preferable to a conservative strategy, mainly because of the halving of refractory or severe angina, and with no increased risk of death or myocardial infarction.

Published online September 1, 2002. http://image.thelancet.com/extras/02art8090web.pdf

Introduction

The most appropriate revascularisation strategy after presentation with unstable angina or non-ST-segmentelevation myocardial infarction remains contentious for patients at moderate risk. The American Heart Association/American College of Cardiology (AHA/ACC) guidelines recommend an invasive strategy for patients at high risk, but specify that either an invasive strategy or a conservative strategy is appropriate for patients at moderate or low risk.1 Nevertheless, in largescale international registries, only 25–28% of patients with non-ST-elevation myocardial infarction and 18% of those with unstable angina undergo percutaneous coronary intervention (PCI) during the initial hospital admission.2, 3 These rates vary by geographic region and availability of PCI facilities (38% in the USA; 29% in Europe; 24% in Argentina and Brazil; and 16% in Australia, New Zealand, and Canada).2

Results of the FRISC II trial (Fragmin and Fast Revascularization during Instability in Coronary artery disease) and the TACTICS-TIMI 18 trial (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy) suggested that an early invasive strategy was indicated if patients had ischaemia on the electrocardiograph or raised biochemical markers of myocardial damage.4, 5, 6 However, findings from these two trials contrasted with the neutral or negative findings from earlier studies.7, 8 Interpretations of these trials are influenced by contemporaneous standards of interventional therapy (instrumentation, stenting, adjunctive therapy, use of internal mammary grafts), improvements in antithrombotic therapy, the extent of separation between strategies in revascularisations, and the definitions of myocardial infarction.

RITA 3 was designed to test the hypothesis that routine early angiography with myocardial revascularisation (as clinically indicated) is better than a conservative strategy in patients with unstable angina or non-ST-elevation myocardial infarction. All patients were to receive optimum medical treatment. Thus, RITA 3 compared two strategies: systematic angiography and, where angiographically indicated, revascularisation versus optimum medical care with ischaemiaprovoked or symptom-provoked angiography and revascularisation.

The definition of myocardial infarction has evolved since the start of RITA 3. The new definition agreed by the European Society of Cardiology (ESC) and ACC/AHA suggests that, with a typical clinical syndrome, a rise and fall of troponin or creatine kinase-MB concentration above the 99th centile of normal controls should constitute myocardial infarction.9 Neither the new definition nor the original WHO definition of myocardial infarction provide justification for a difference in the threshold for troponin (or cardiac enzyme) concentration for the diagnosis of myocardial infarction between patients who have had PCI and those who have not. Thus, by contrast with FRISC II and TACTICS-TIMI 18, in which the threshold for diagnosis of myocardial infarction differed between those undergoing revascularisation (PCI or coronary-artery bypass grafting [CABG]) and those treated conservatively, RITA 3 used a common definition for myocardial infarction irrespective of treatment strategy. This issue is important in the interpretation and comparison of trials of intervention in acute coronary syndromes.10, 11, 12, 13

Section snippets

Patients

From Nov 12, 1997, to Oct 2, 2001, we enrolled patients from 45 hospitals in England and Scotland, UK. Most hospitals (n=37) were district or community hospitals without revascularisation facilities on site. 19 centres served as the referral intervention sites, eight of which also served as recruitment centres.

Patients were eligible for inclusion if they had suspected cardiac chest pain at rest and had documented evidence of coronary artery disease with at least one of: evidence of ischaemia on

Results

1810 patients were randomised: 895 to intervention and 915 to conservative management (figure 1). One patient in the conservative group emigrated 4 months after randomisation and was not traced for follow-up or survival status at 1 year. Another patient, also in the conservative group, is a member of the Armed Forces and is known to be alive but was not available for follow-up at 1 year. Three patients were withdrawn immediately after telephone randomisation because they failed the inclusion

Discussion

RITA 3 shows that an interventional strategy results in a significant reduction in the combined endpoint of death, non-fatal myocardial infarction, or refractory angina. The main effect was on refractory angina. The definition of refractory angina in our study was stringent, and during the index admission required recurrence of ischaemic pain at rest or on minimum exertion, despite maximum medical treatment, associated with new electrocardiographic changes and prompting revascularisation within

References (22)

  • L Wallentin et al.

    Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial

    Lancet

    (2000)
  • W Markiewicz

    Management of unstable coronary-artery disease

    Lancet

    (2000)
  • E Braunwald et al.

    ACC/AHA guidelines for the management of patients with unstable angina and non ST segment elevation myocardial infarction: executive summary and recommendations

    Circulation

    (2000)
  • KAA Fox et al.

    Management of acute coronary syndromes: variations in practice and outcome. Findings of the Global Registry of Acute Coronary Events (GRACE)

    Eur Heart J

    (2002)
  • D Hasdai et al.

    A prospective survey of acute coronary syndromes (Euro Heart Survey ACS)

    Eur Heart J

    (2002)
  • FRiSC II prospective randomised multicentre study

    Lancet

    (1999)
  • CP Cannon et al.

    Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban

    N Engl J Med

    (2001)
  • Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction: results of the TIMI IIIB Trial

    Circulation

    (1994)
  • WE Boden et al.

    The Veterans Affairs non-Q-wave infarction strategy: outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy

    N Engl J Med

    (1998)
  • Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial infarction

    Eur Heart J

    (2000)
  • M Flather et al.

    Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes

    N Engl J Med

    (2001)
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